Opiate receptors, which are important pharmacological targets for analgesia and for the control of drug addiction, have not been cloned and their amino acid sequences are unknown. Recent work indicates that several opiate receptor subtypes are coupled to G protein second messenger systems. Therefore, it appears that these receptor subtypes are members of the rapidly growing superfamily of 7 transmembrane domain receptors. Recent advances in cloning technology, coupled with our large and rapidly growing data base on G protein-coupled receptors, have provided new pathways to the cloning of opiate receptors. In this application we propose several cloning strategies which make use of recent advances in the cloning of G protein-coupled receptors. In Phase II of this program, we plan to complete the cloning and characterization of these opiate receptor subtypes, including the development of heterologous expression systems for each isolated clone. These expression systems will provide the basis for the design and testing of selective, high affinity drugs targeted to individual human receptor subtypes.